(1) Field of the Invention
The present invention relates to a method for inhibiting a tumor particularly by feeding a mammal a composition comprising anthocyanins. In particular, the compositions of anthocyanins inhibit intestinal adenomas.
(2) Description of Related Art
Tumors occur in mammals and can be life threatening. In humans this can include prostate, colon, breast, lung, and kidney, prostate, liver, lymphoma/CNS, leukemia, pancreatic, gastric, esophageal, ovarian, uterine and testicular tumors, for instance.
Colon cancer is the second most common cause of cancer mortality and the fourth most common in incidence in the United States (American Cancer Society, Cancer Facts and Figures 1997). Diet has been considered to account for 30% of incidence of colon cancer (Doll and Peto, J. Natl Cancer Inst 66:1192-1308 (1981)). Epidemiological studies have shown consuming fruits and vegetables lowers incidences of various cancers including colon cancer. This anticancer effect of fruits and vegetables is thought to be due in part to antioxidant effects of phytochemicals (Stavric, B., Clin Biochem 27:319-332 (1994)). Other potential anticancer mechanisms are inhibition of carcinogen formation, blocking biotransforming enzyme actions, inducing oxidative detoxification, and trapping and scavenging electrophilic agents (Stavric, B., Clin Biochem 27:319-332 (1994)).
Tart cherries contain various phytochemicals including anthocyanins and cyanidin. Anthocyanins are flavonoid pigments in many fruits and vegetables as well as cherries. Cyanidin is the major aglycone in cherries and its glycosylated form provides the anthocyanins. All anthocyanins are derivatives of the basic flavylium cation structure. Montmorency and Balaton cherries contain 120 and 220 mg/g, respectively, of anthocyanins (Wang, H., et al, J. Nat Prod 62:86-88 (1999)). These anthocyanins have been found to be antioxidants of lipids, particularly in foods as described in U.S. Pat. No. 5,985,636 to Gray et al., and inhibit cyclooxygenase enzymes as described in U.S. application Ser. No. 09/337,313, filed Jun. 21, 1999. In this study, cyanidin was intermediate in efficacy between aspirin and the non-steroidal anti-inflammatory drug, flurbiprofen. The anthocyanins are labile to heating and drying destroys their effectiveness.
The Min mouse has been proposed to be a model for the study of human colorectal cancer (Moser, A. R., et al, Science 247:322-324 (1990)). A mutant mouse lineage predisposed to multiple intestinal neoplasia (Min) results from a mutation in the murine homolog of the adenomatous polyposis coli (APC) gene (Su, L. K., et al, science 256:668-670 (1992)). The APC gene is also mutated in humans who develop sporadic colon cancer as well as persons with familial adenomatosis polyposis (FAP), an autosomal dominantly inherited disease that predisposes to colorectal cancer. The primary phenotype of mice carrying this mutation appears to be the development of multiple adenomas, which progress to adenocarcinomas of the intestine in older mice. Min is transmitted by affected mice to 50% of progeny with an unbiased sex distribution, as is characteristic of a fully penetrant autosomal dominant trait (Moser, A. R., et al, Science 247:322-324 (1990)). The Min mouse strain is an excellent animal model for the anticarcinogenic potential of dietary factors and other potential cancer therapeutic agents (e.g. NSAIDS).
Non-steroidal anti-inflammatory drugs (NSAIDs) that inhibit cyclooxygenase (COX) enzymes have been found to possess preventive effects for colon cancer. Research on the NSAIDs sulindac and proxicam in Min mice showed that they reduced the incidence of intestinal tumors (Boolbol, S. K., et al, Cancer Res. 56:2556-2560 (1996); Jacoby, R. F., et al, Cancer Res. 56:710-714 (1996)).
There is a need for a method of treatment which does not involve NSAIDS and is based upon a phytoceutical.
The present invention relates to a method for inhibiting a tumor which comprises: providing a composition comprising an anthocyanin from a berry or cyanidin in contact with the tumor over a period of time sufficient to inhibit the tumor.
The inhibition can be in vivo or in vitro. The compositions can contain bioflavonoids and phenolics naturally present in the berry.
The present invention also relates to a method for inhibiting a tumor in a mammal which comprises: feeding the mammal a composition comprising an anthocyanin from a berry or cyanidin in an amount and for a period of time sufficient to inhibit the tumor.
Further, the present invention relates to a method for inhibiting intestinal adenomas in a mammal which comprises: feeding the mammal a composition comprising an anthocyanin from cherries or cyanidin in an amount and for a period of time sufficient to inhibit the intestinal adenomas.
Anthocyanins are flavonoid pigments in blue and red fruits and vegetables including cherries. Cyanidin is the primary aglycone form of tart cherry anthocyanin. The dosage amount is preferably between about 0.1 and 300 mg per day per kg of body weight of the mammal.
Preferably the anthocyanins are between about 70% to 100% by weight of the composition, with the balance, if present, being the phenolics and the bioflavonoids. U.S. Pat. No. 5,985,636 to Gray et al describes the isolation of the anthocyanins in detail.
The compositions of the present invention can be combined with other active agents which have antitumor properties to provide greater effectiveness. These include NSAIDS.
The term xe2x80x9cinhibitingxe2x80x9d means preventing the formation of the tumor and/or causing the tumor to shrink. The term xe2x80x9ctumorxe2x80x9d includes carcinomas, sarcomas and lymphoid tumors.
The compounds of the present invention can be applied topically or can be fed orally depending upon the type of tumor. Enteral administration can be via nasogastric tube or percutaneous enterogastrostomy (PEG). Parenteral administration can be by administration (peripheral or central). They can also be injected into the tumor. In each instance a suitable carrier and an adjuvant is included where necessary.
The term xe2x80x9canthocyaninsxe2x80x9d means the compounds that impart color in berries.
The term xe2x80x9cbioflavonoidsxe2x80x9d means the isoflavonoids and flavonoid compounds contained in berries.
The term xe2x80x9cphenolicsxe2x80x9d refers to compounds with a phenyl group and having one or more hydroxyl groups from berries.
It is therefore an object of the present invention to provide a natural source berry composition which can be used as an antitumor agent. It is further an object of the present invention to provide naturally a occurring phytoceutical which is inexpensive to prepare. These and other objects will become increasingly apparent by reference to the following description and the drawings.